Biology subjects

Becker, J.

Publications and source records attributed to Becker, J..

42 records · Page 3Linked to original sources

bioRxiv2020

Active outer hair cell motility can suppress vibrations in the organ of Corti

High sensitivity and selectivity of hearing require active cochlea. The cochlear sensory epithelium, the organ of Corti, vibrates due to external and internal excitations. The external stimulation is acoustic pressures mediated by the scala fluids, while the internal excitation is generated by a type of sensory receptor cells (the outer hair cells) in response to the acoustical vibrations. The outer hair cells are cellular actuators that are responsible for cochlear amplification. The organ of Corti is highly structured for transmitting vibrations originating from acoustic pressure and active outer hair cell force to the inner hair cells that synapse on afferent nerves. Understanding how the organ of Corti vibrates due to acoustic pressure and outer hair cell force is critical for explaining cochlear function. In this study, excised cochlear turns were freshly isolated from young gerbils. The organ of Corti in the excised cochlea was subjected to mechanical and electrical stimulation that are analogous to acoustical and cellular stimulation in the natural cochlea. Organ of Corti vibrations including those of individual outer hair cells were measured using optical coherence tomography. Respective vibration patterns due to mechanical and electrical stimulation were characterized. Interactions between the two vibration patterns were investigated by applying the two forms of stimulation simultaneously. Our results show that the interactions could be either constructive or destructive, which implies that the outer hair cells can either amplify or suppress vibrations in the organ of Corti. We discuss a potential consequence of the two interaction modes for cochlear frequency tuning. Statement of SignificanceThe function of the mammalian cochlea is characterized by sharp tuning and high-level of amplification. Both tuning and amplification are achieved mechanically through the action of cellular actuators in the sensory epithelium. According to widely accepted theory, cochlear tuning is achieved by selectively amplifying acoustic vibrations. This study presents a set of data suggesting that the cochlear actuators can both amplify and suppress vibrations to enhance cochlear tuning. Presented results will explain why the actuator cells in the cochlea spend energy in the locations where there is no need for amplification.

neuroscience↗

bioRxiv2019

PSF broadening due to fluorescence emission

Fluorescent structures are nowadays commonly used in the field of biological imaging. However the emission of fluorescence is always given within a finite spectrum. When the imaging systems point spread function is measured, this can be described as an incoherent summation of individual single-wavelength PSFs, weighted by the emission spectrum. As the full-width-half-maximum of the PSF scales inversely with the wavelength and most emission spectra exhibit a fluorescence tail at longer wave-lengths, this contributes significantly to lateral broadening. In our work we theoretically quantify this effect by deriving an analytic expression, which has been verified against some numerical simulations (rel. error on average 3 %). We report a FWHM-broadening on the order of 10 nm and additionally propose a way to overcome this broadening by splitting the emission spectrum into multiple wavelength segments. The corresponding image data is recombined in Fourier space by weighted averaging, leading to an improved signal-to-noise ratio at high spatial frequencies and a reduction of the FWHM of up to 8 nm (relative reduction of the broadening by {approx} 70 %). We also introduce a corrected wavelength, which in combination with already existing PSF calculation tools, describes a theoretical PSF which incorporates the aforementioned broadening effect.

biophysics↗

bioRxiv2018

Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/{beta}-catenin, TGF-{beta} and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

genetics↗

bioRxiv2018

Kingdom-wide comparison reveals conserved diurnal gene expression in Archaeplastida

Plants have adapted to the diurnal light-dark cycle by establishing elaborate transcriptional programs that coordinate innumerable metabolic, physiological, and developmental responses to the external environment. These transcriptional programs have been studied in only a few species, and their function and conservation across algae and plants is currently unknown. We performed a comparative transcriptome analysis of the diurnal cycle of nine members of Archaeplastida, and we observed that, despite large phylogenetic distances and dramatic differences in morphology and lifestyle, diurnal transcriptional programs of these organisms are similar. However, the establishment of multicellularity coincided with the uncoupling of cell division from the diurnal cycle and decreased diurnal control of the expression of the biological pathways. Hence, our study provides evidence for the universality of diurnal gene expression and elucidates its evolutionary history among different photosynthetic eukaryotes.

evolutionary biology↗

bioRxiv2018

Non-Canonical Activation of CREB Mediates Neuroprotection in a C. elegans Model of Excitotoxic Necrosis

Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-Receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways. The strongest evidence involves activation of the transcription factor cAMP Response Element Binding-protein (CREB), widely recognized for its importance in synaptic plasticity. Canonical views describe CREB as a phosphorylation-triggered transcription factor, where transcriptional activation involves CREB phosphorylation and association with CREB Binding Protein (CBP). However, given CREBs ubiquitous cross-tissue expression, the multitude of cascades leading to CREB phosphorylation, and its ability to regulate thousands of genes, it remains unclear how CREB exerts closely-tailored, differential neuroprotective responses in excitotoxicity. A non-canonical, alternative cascade for activation of CREB-mediated transcription involves the CREB co-factor cAMP-regulated transcriptional co-activator (CRTC), and may be independent of CREB phosphorylation. To identify cascades that activate CREB in excitotoxicity we use a C. elegans model of neurodegeneration by excitotoxic necrosis. We demonstrate that CREBs neuroprotective effect is conserved, and seems most effective in neurons with moderate Glu exposure. We find that factors mediating canonical CREB activation are not involved. Instead, phosphorylation-independent CREB activation in nematode excitotoxic necrosis hinges on CRTC. CREB-mediated transcription that depends on CRTC, but not on CREB phosphorylation, might lead to expression of a specific subset of neuroprotective genes. Elucidating conserved mechanisms of excitotoxicity-specific CREB activation can help us focus on core neuroprotective programs in excitotoxicity.

neuroscience↗

bioRxiv2017

Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations

The immune system plays a major role in human health and disease, and understanding genetic causes of interindividual variability of immune responses is vital. We isolated monocytes from 134 genotyped individuals, stimulated the cells with three defined microbe-associated molecular patterns (LPS, MDP, and ppp-dsRNA), and profiled the transcriptome at three time points. After mapping expression quantitative trait loci (eQTL), we identified 417 response eQTLs (reQTLs) with differing effect between the conditions. We characterized the dynamics of genetic regulation on early and late immune response, and observed an enrichment of reQTLs in distal cis-regulatory elements. Response eQTLs are also enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover novel reQTL effects in multiple GWAS loci, and show a stronger enrichment of response than constant eQTLs in GWAS signals of several autoimmune diseases. This demonstrates the importance of infectious stimuli modifying genetic predisposition to disease.

genetics↗